Abstract
Molecules that contain one or more fluorine atoms are crucial to drug discovery. There are protocols available for the selective synthesis of different organofluorine compounds, including those with a fluoro-substituted or a trifluoromethyl-substituted stereogenic carbon centre. However, approaches for synthesizing compounds with a trifluoromethyl- and fluoro-substituent stereogenic carbon centre are far less common. This potentially impactful set of molecules thus remains severely underdeveloped. Here we introduce a catalytic regio-, diastereo- and enantioselective strategy for the preparation of homoallylic alcohols bearing a stereogenic carbon centre bound to a trifluoromethyl group and a fluorine atom. The process, which involves a polyfluoroallyl boronate and is catalysed by an in situ-formed organozinc complex, can be used for diastereodivergent preparation of tetrafluoro-monosaccharides, including ribose core analogues of the antiviral drug sofosbuvir (Sovaldi). Unexpected reactivity/selectivity profiles, probably originating from the trifluoromethyl- and fluoro-substituted carbon site, are discovered, foreshadowing other unique chemistries that remain unknown.